Clinical radiation dose prescriptions for spinal radiosurgery have been escalated to levels currently accepted in intracranial radiosurgery with the expectation of increasing the durability of tumor control in the spinal column and reducing tumor induced paralysis and pain but the maximum single-dose a vertebra can tolerate with structural integrity intact is unknown and may be exceeded in current prescriptions. A study is currently underway to determine the radiation dose-related incidence of spinal cord myelopathy in swine that receive a spinal radiosurgery treatment but analysis of radiation sequelae is limited to neurologic tissue. A concurrent, synergistic study will dramatically expand the utility of the current study by investigating radiation dose-related bone toxicity and its affect on biomechanical bone strength. Predictive indicators of the risk of vertebral fracture following radiation therapy will be learned through data collected by three advanced imaging modalities (micro-CT, quantitative CT and PET) and by blood serum analysis, bone histomorphometry and biomechanical compression testing in a preclinical model. Dose-dependent changes in blood flow, metabolic activity, bone density, microarchitecture, and bone turnover will be characterized for a one year period after radiosurgery and will be correlated with biomechanical bone strength. Resulting data will provide a rational basis to escalate spinal dose in an informed manner and will likely reveal the radiation-induced pathogenesis of bone weakening so that interventional opportunities can be exploited. Results will ultimately translate into spine cancer patients receiving the best chance for survival with a pain free, high quality of life while maintaining a very low rate of morbidity. PUBLIC HEALTH RELEVANCE: Clinical radiation dose prescriptions for spinal radiosurgery have been escalated to levels currently accepted in intracranial radiosurgery with the expectation of increasing the durability of tumor control in the spinal column and reducing tumor induced paralysis and pain but the maximum single-dose a vertebra can tolerate with structural integrity intact is unknown and may be exceeded in current prescriptions. A study is proposed to investigate radiation dose-related bone toxicity and its affect on biomechanical bone strength. The proposed study will likely lead to predictive indicators of the risk of vertebral fracture following radiation therapy and will reveal the radiation-induced pathogenesis of bone weakening so that interventional opportunities can be exploited.